This proposal is designed to provide the candidate with basic science training in molecular biology so that he may investigate gastrointestinal or hepatic pathophysiology at the molecular level. Phase I of the program will consist of intensive training in the laboratory of Dr. Frederick W. Alt in the Department of Biochemistry and Molecular Biophysics of the Columbia University College of Physicians and Surgeons. The candidate will join a broad effort to characterize the mechanism and regulation of Ig gene rearrangements. This will acquaint him with laboratory techniques in molecular biology and concepts of gene regulation and immunology. The candidate will also attend a limited number of graduate courses in biochemistry which will broaden these concepts and demonstrate their applicability to various biological systems. During phase II, Dr. Michael Field (sponsor), Director of the Division of Gastroenterology, Dr. Qais Al-Awqati, Director of the Division of Nephrology and Co-Director of Columbia's Physician Scientists Program Award, Dr. Robert M. Glickman, Chairman of the Department of Medicine and Dr. Frederick W. Alt will jointly supervise the candidate's transition to and progress in the Department of Medicine where he will join a productive GI Division and embark on more clinically oriented studies. Dr. Alt's experience in training physician-scientists (there are two Physician scientist Awardees in his laboratory now) will allow him to continue to guide the candidate's research. While it is premature to outline specific phase II projects at this time, the candidate will use skills acquired during Phase I to investigate a clinically relevant process such as metabolic regulation, malignant transformation or chronic inflammation in the GI tract and liver. Upon completion of his training, the candidate will be able to join a growing faculty of junior and senior investigators in the Division of Gastroenterology, enabling him to combine a major commitment to basic research with a modest amount of clinical teaching and interactions.